Methods of using dyphylline for the promotion of hair growth

ABSTRACT

The subject invention relates to methods for promoting hair growth in mammals comprising topical application of dyphylline or a pharmaceutically-acceptable salt thereof. The subject invention further involves topical compositions comprising dyphylline.

TECHNICAL FIELD

The subject invention relates to the field of regulating hair growth inmammalian skin. Specifically, the subject invention relates to methodsfor the promotion of hair growth in humans.

BACKGROUND

Society in general continues to attach a stigma to hair loss. Men andwomen suffer from hair loss, often resulting in self-consciousnessrelating to the hair loss. Domestic animals, such as cats and dogs, alsosuffer from hair loss. While the animal is not likely to be emotionallyaffected by such hair loss, its owner may be, particularly if such ananimal is to be shown in various competitions. Additionally, increasedhair growth in livestock such as sheep, thereby resulting in increasedwool production, is also desirable. The desire for a healthy full head(or body, in the case of animals) of hair has resulted in a variety ofapproaches to the "curing" of hair loss.

One such approach involves the much publicized use of minoxidil(6-(1-piperidinyl)-2,4-pyrimidinediamine 3-oxide), a potentantihypertensive agent, as a hair growth promoting agent (see U.S. Pat.Nos., 3,461,461; 3,973,061; 3,464,987; and 4,139,619). Unfortunately,not all people respond to minoxidil and the efficacy level is limited inthose individuals exhibiting a response.

Another approach for "curing" hair loss involves a procedure of weavingsynthetic or natural hair strands into the remaining hair strands of thesubject. Such a procedure is time consuming, expensive and requiresfollow-up re-weavings as the weaves loosen and/or the subject's existinghair strands grow. Furthermore, such a procedure does not cure hairloss, but merely masks the condition.

Another approach for treating hair loss is the use of hair plugs. Thisprocedure involves the transplantation of terminal hair follicles fromregions of normal hair growth on the subject's scalp to regions ofthinning or no hair growth on the scalp. The procedure is timeconsuming, expensive and can be painful. Furthermore, the transplantedplugs, at least in the early stages following transplantation, producean unnatural look to the scalp.

For the foregoing reasons, there is a need for an easily administered,efficacious agent for treating hair loss in a mammal having little or noundesirable side effects. It is an object of the subject invention toprovide topical compositions for promoting hair growth and/or treatinghair loss in mammalian skin or scalp. It is a further object of thesubject invention to provide such compositions which are gentler andless irritating to the skin than existing compositions. It is also anobject of the subject invention to provide methods for promoting hairgrowth and/or treating hair loss in mammalian skin or scalp.

SUMMARY OF THE INVENTION

The subject invention involves dyphylline chemical name of dyphyllineand compositions comprising dyphylline. Such a compound and compositionssatisfy the need for an efficacious, easily administered agent forregulating hair growth, having little or no undesirable side effects.The subject invention is also directed to a method of regulating hairgrowth in a mammal (e.g., humans and domestic animals) susceptible to orsuffering from hair loss, comprising application of a composition of thesubject invention.

The compositions of the subject invention comprise a safe and effectiveamount of dyphylline and a pharmaceutically-acceptable carrier.

These and other features, aspects and advantages of the subjectinvention will become better understood with reference to the followingdescription and appended claims.

DETAILED DESCRIPTION OF THE INVENTION

It has been found that compositions containing dyphylline exhibit theability to regulate hair growth in mammalian skin and scalp, withoutundesirable side effects, such as skin irritation, commonly associatedwith known compositions for regulating hair growth. While the subjectinvention is not limited to any particular mode of action, it isbelieved that dyphylline may regulate hair growth by elevatingintracellular level of cyclic adenosine monophosphate, via inhibitingphosphodiesterase and activating adenosine reception on all membrane. Byphosphodiesterase inhibition which results in an increase in the levelof intracellular cyclic adenosine monophosphate (cAMP). Reduction ofcAMP levels in the hair follicle has been linked to alopecia or hairloss.

As used herein, "dyphylline" means a compound having the structure:##STR1##

As used herein, "topical application" means directly laying on orspreading on outer skin.

As used herein, "cutaneous injection" means introduction of a substancebeneath or within the skin by a hypodermic needle; preferably proximateto the site of desired response.

As used herein, "safe and effective amount" means a sufficient amount ofa compound or composition to significantly induce a positivemodification in the condition being treated, but low enough to avoidserious side effects.

As used herein, "comprising" means that other steps and otheringredients which do not affect the end result can be added. This termencompasses the terms "consisting of" and "consisting essentially of".

As used herein, "pharmaceutically-acceptable" means that drugs,medicaments or inert ingredients which the term describes are suitablefor use in contact with the tissues of humans and lower animals withoutundue toxicity, incompatibility, instability, irritation, allergicresponse, and the like.

As used herein, "cosmetically-acceptable" means that ingredients whichthe term describes are suitable for use in contact with the skin ofhumans and lower animals without undue toxicity, incompatibility,instability, irritation, allergic response, and the like.

As used herein, "regulating hair growth" means increasing the rate ofhair growth and/or inducing the formation of a greater number of hairstrands, and/or increasing the diameter of the hair strand, and/orlengthening the hair strand, and/or changing the hair follicle fromvellus to terminal, and/or converting follicles from telogen to anagenphase (thereby increasing the overall ratio of anagen phase folliclesrelative to telogen phase follicles) and/or preventing, retarding, orarresting the process of hair loss, and/or treating alopecias.

As used herein, "vellus hair follicle" means a hair follicle whichproduces a soft, short, and often colorless hair fiber. The size of thevellus follicle is considerably smaller than the terminal hair follicle.In an adult, vellus follicles can be found on the forehead (i.e.,receding hair line area) and bald scalp beside other parts of the body.

As used herein, "terminal follicle" means a hair follicle which producesa coarse, long, and often pigmented hair follicle. The size of theterminal follicle is considerably larger, thicker in diameter and longerthan the vellus follicle. In the adult, terminal follicles can be foundon the scalp, axilla and pubic areas. (Chest and legs.)

As used herein, "anagen phase" refers to the period in the hair folliclegrowth cycle wherein the follicle is actively growing and a real hairstrand is extending.

As used herein, "telogen phase" refers to the period in the hair growthcycle wherein the follicle is resting and hair strand cease extending.

Compositions useful for regulating hair growth preferably comprise fromabout 0.005% to about 15% of dyphylline, more preferably from about 0.1%to about 10%, more preferably still from about 1% to about 5%, morepreferably still from about 1% to about 3%.

The Carrier

The compositions of the subject invention comprise a solid, semi-solidor liquid cosmetically and/or physiologically acceptable and/orpharmaceutically-acceptable carrier to enable dyphylline to be deliveredto the desired target at an appropriate concentration. The carrier canitself be inert or it can possess cosmetic, physiological orpharmaceutical benefits of its own. The nature of the carrier will bedictated by the method chosen for administration of the composition. Themethod of administration of dyphylline composition may range frominternal methods such as injection to external topical methods.

A preferred method of administration of dyphylline is by cutaneousinjection. The carrier for facilitation of such administration wouldpreferably comprise water or a saline solution, preferably an isotonicsaline solution.

A more preferred method of administration of dyphylline is by topicalapplication. Topical application is preferably achieved withcompositions in the forms of lotions, solutions, ointments, sprays,tonics, creams, bars, shampoos, cream rinses, gels, sticks, mousse,pastes and the like.

Topical compositions of the subject invention can be formulated asliquids, for example as a lotion, shampoo, conditioner, mousse or milk.Such liquid compositions may be formulated for use in conjunction withan applicator such as a roll-ball applicator, a tined applicator, a padapplicator, or a spray device such as an aerosol can containingpropellant, or a container fitted with a pump to dispense the liquidproduct, or a liquid-impregnated fabric, such as a tissue wipe.

Alternatively, the compositions of the invention can be solid orsemi-solid, for example sticks, creams or gels. Such solid or semi-solidcompositions may be formulated for use in conjunction with a suitableapplicator or simply a tube, jar or other convenient container.

The selection of a carrier for this purpose subjects a wide range ofpossibilities depending on the required product form of the composition.Suitable vehicles can be classified as described hereinafter.

The term "topical carrier" refers to substances which can act asdiluents, dispersants, or solvents for dyphylline which therefore ensurethat it can be applied to and distributed evenly over the selectedtarget at an appropriate concentration. The carrier is preferably onewhich can aid penetration of dyphylline into the skin to reach theimmediate environment of the hair follicle. Topical carriers useful incompositions of the subject invention can include water as a vehicle,and/or at least one cosmetically acceptable vehicle other than water.Carriers useful in topical compositions according to the invention mayinclude liposomes, latex latices, microspheres, cyclodextrins andvarious forms of microencapsulation of dyphylline. A preferred amount ofpenetration enhancing agent is from about 1% to about 5% of thecomposition.

Generally, the carrier is either organic in nature or an aqueousemulsion and capable of having dyphylline dispersed or dissolvedtherein. The carrier may include pharmaceutically-acceptable emollients,skin penetration enhancers, coloring agents, fragrances, emulsifiers,thickening agents, and solvents.

Topical compositions of the subject invention may be formulated as acomposition comprising an emollient. Such compositions typicallycomprise from about 1% to about 50%, preferably from about 5% to about20% of a topical pharmaceutically-acceptable emollient; and a safe andeffective amount of dyphylline.

As used herein, "emollients" refer to materials used for the preventionor relief of dryness, as well as for the protection of the skin. A widevariety of suitable emollients are known and may be used herein. Suchemollients include, but are not limited to, hydrocarbon oils and waxes,silicon oils, triglyceride fats and oils, acetoglyceride esters,ethoxylated glycerides, alkyl esters of fatty acids having 10 to 20carbon atoms, alkenyl esters of fatty acids having 10 to 20 carbonatoms, fatty acids having 8-22 carbon atoms, fatty alcohols having 8-22carbon atoms, fatty alcohol ethers, ether-esters, lanolin andderivatives, polyhydric alcohols and polyether derivatives, wax esters,beeswax derivatives, vegetable waxes, phospholipids, sterols, andamides. SAGARIN, COSMETICS, SCIENCE AND TECHNOLOGY, 2nd Edition, Vol. 1,pp. 32-43 (1972), incorporated herein by reference, contains numerousexamples of suitable materials.

Topical compositions of the subject invention may also be formulated asa cream. Preferably the creams of the present invention comprise a safeand effective amount of dyphylline; from about 1% to about 50%,preferably from about 5% to about 25%, of an emollient; and from about25% to about 95% water. Optionally the cream form contains a suitableemulsifier. When an emulsifier is included, it is in the composition ata level from about 1% to about 25%, preferably from about 3% to about10%. Emulsifiers may be nonionic, anionic or cationic. Suitableemulsifiers are disclosed in, for example, U.S. Pat. No. 3,755,560,issued Aug. 28, 1973, Diekert et al.; U.S. Pat. No. 4,421,769,issuedDec. 20, 1983, Dixon et al.; and McCutheon's Detergents and Emulsifiers,North American Edition, pp. 317-324 (1986); the disclosures of which areincorporated herein by reference. Preferred emulsifiers are anionic ornonionic.

Topical compositions of the subject invention may also be formulated asa composition comprising a lotion. Preferably the lotions of the subjectinvention comprise a safe and effective amount of dyphylline; from about1% to about 50%, preferably from about 3% to about 15% of an emollient;and from about 45% to about 85%, preferably from about 50% to about 75%water. Optionally, the lotion form may contain a suitable emulsifier,comprising from about 1% to about 50%, preferably from about 3% to about10% of the composition. Example of suitable emulsifiers are includedhereinabove in the disclosure of cream formulations.

Preferably a solution form of the present invention comprises a safe andeffective amount of dyphylline, water and a suitable organic solvent.Suitable organic materials useful as the solvent or a part of a solventsystem are as follows: propylene glycol, dimethyl isosorbide, N-octylpyrrolidone, glycerin, polyethylene glycol (M.W. 200-600), polypropyleneglycol (M.W. 425-2025), sorbitol esters, 1,2,6-hexanetriol, ethanol,isopropanol, diethyl tartrate, butanediol, and mixtures thereof.

Gel compositions of the present invention can be formulated by simplymixing a suitable thickening agent to the previously described solutioncompositions. The gel compositions preferably comprise a safe andeffective amount of dyphylline; from about 5% to about 75%, preferablyfrom about 10% to about 50%, of an organic solvent as previouslydescribed for solutions; and from about 0.1% to about 10%, preferablyfrom about 0.5% to about 5% of the thickening agent.

Compositions of solid forms of the present invention have use asstick-type compositions intended for application to scalp or other partsof the body. Such compositions preferably comprise a safe and effectiveamount of dyphylline, and from about 50% to about 98%, preferably fromabout 60% to about 90%, of the previously described emollients. Suchcompositions can further comprise from about 1% to about 20%, preferablyfrom about 5% to about 15%, of a suitable thickening agent, andoptionally emulsifiers and water.

Scalp cleaning compositions useful in hair growth regulation, comprise,in addition to dyphylline, a cosmetically-acceptable surfactant. Thecleaning compositions useful in the subject invention preferably containa safe and effective amount of dyphylline and preferably from about 1%to about 90%, more preferably from about 5% to about 10%, of acosmetically-acceptable surfactant.

The physical form of the cleansing compositions is not critical. Thecompositions can be, for example, formulated as toilet bars, liquids,shampoos, pastes, or mousses. Rinse-off cleansing compositions, such asshampoos, require a delivery system adequate to deposit an effectiveamount of dyphylline to the scalp. A preferred delivery system involvesthe use of insoluble complexes. For a more complete disclosure, see U.S.Pat. No. 4,835,148, Barford et al., issued May 30, 1989; incorporatedherein by reference in its entirety.

The surfactant component of the compositions useful in the subjectinvention are selected from anionic, nonionic, zwitterionic, amphotericand ampholytic surfactants, as well as mixtures of these surfactants.Such surfactants are well-known to those skilled in the detergency art.

The cleaning compositions useful in the subject invention can optionallycontain, at their ann-established levels, materials which areconventionally used in cleansing compositions. Nonlimiting examples ofpossible surfactants include isoceteth-20, sodium methyl cocoyl taurate,sodium methyl oleoyl taurate, and sodium lauryl sulfate. See U.S. Pat.No. 4,800,197, to Kowcz et al., issued Jan. 24, 1989, which isincorporated herein by reference in its entirety. Examples of a broadvariety of additional surfactants useful herein are described inMcCutcheon's, DETERGENTS AND EMULSIFIERS, North American Edition (1986),published by Allured Publishing Corporation, which is incorporatedherein by reference in its entirety.

Combination Actives

The compositions of the subject invention useful for regulating hairgrowth may also optionally comprise other hair growth stimulants capableof functioning in different ways to enhance the benefit of dyphylline.An example of such a substance includes, but is not limited tominoxidil, and derivatives thereof, as disclosed in U.S. Pat. Nos.,3,461,461; 3,973,061; 3,464,987; and 4,139,619; incorporated herein byreference.

Additional hair growth stimulants useful in compositions of the subjectinvention comprising dyphylline include the agents disclosed by thefollowing, which are all incorporated herein by reference: U.S. Pat. No.5,215,760, Kavoussi and Kavoussi, issued Jun. 1, 1993; U.S. Pat. No.5,192,534, Grollier and Richoux, issued Mar. 9, 1993; U.S. Pat. No.5,178,883, Knighton, issued Jan. 12, 1993; U.S. Pat. No. 5,177,061,Pickart, issued Jan. 5, 1993; U.S. Pat. No. 5,130,142, Wong and Warren,issued Jul. 14, 1992; U.S. Pat. No. 5,068,315, Buultjens, Colin, Jahodaand Oliver, issued Nov. 26, 1991; U.S. Pat. No. 5,091,173, Buultjens,Hellens, Oliver and Withers, issued Feb. 25, 1992; U.S. Pat. No.5,037,643, Green, issued Aug. 6, 1991; U.S. Pat. No. 4,975,441, Gibson,issued Dec. 4, 1990; U.S. Pat. No. 4,871,839, Gibson, issued Oct. 3,1989; U.S. Pat. No. 4,832,946, Green, issued May 23, 1989; U.S. Pat. No.4,761,401, Couchman, issued Aug. 2, 1988; U.S. Pat. No. 4,139,619,Chidsey, issued Feb. 13, 1979; U.S. Pat. No. 3,466,364, Takahashi,issued Sep. 9, 1969; and U.S. Pat. No. 1,732,120, Christen, issued Oct.15, 1929; PROSCAR™ (a.k.a., finasteride or (5α,17β)-1-1-Dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide; Merck &Co.) see THE MERCK INDEX, 11th Ed., p. 1250, entry 7888; and cyproteroneacetate, see THE MERCK INDEX, 11 th Ed., p. 435, entry 2781.

Delivery Methods for Topical Compositions

The topical compositions useful for the methods of the instant inventioncan be delivered from a variety of delivery devices. The following aretwo nonlimiting examples.

A. Medicated cleansing pads

The compositions useful herein can be incorporated into a medicatedcleansing pad. Preferably these pads comprise from about 50% to about75% by weight of one or more layers of nonwoven fabric material and fromabout 20% to about 50% by weight of a liquid composition deliverablefrom the nonwoven fabric material preferably comprising from about 0.01%to about 10% dyphylline, more preferably from about 0.5% to about 5%dyphylline, more preferably still from about 1% to about 3%. These padsare described in detail in U.S. Pat. Nos. 4,891,228, to Thaman et al.,issued Jan. 2, 1990; and 4,891,227, to Thaman et al., issued Jan. 2,1990; both of which are incorporated by reference.

B. Dispensing devices

The compositions useful herein can also be incorporated into anddelivered from a soft-tipped or flexible dispensing device. Thesedevices are useful for the controlled delivery of the compositions tothe skin or scalp surface and have the advantage that the treatmentcomposition itself never need be directly handled by the user.Nonlimiting examples of these devices comprise a fluid containerincluding a mouth, an applicator, means for holding the applicator inthe mouth of the container, and a normally closed pressure-responsivevalve for permitting the flow of fluid from the container to theapplicator upon the application of pressure to the valve. The fluidpreferably contains from about 0.005% to about 15% dyphylline, morepreferably from about 0.5% to about 3% dyphylline, more preferably stillfrom about 1% to about 3%.

The valve can include a diaphragm formed from an elastically fluidimpermeable material with a plurality of non-intersecting arcuate slitstherein, where each slit has a base which is intersected by at least oneother slit, and where each slit is out of intersecting relation with itsown base, and wherein there is a means for disposing the valve in thecontainer inside of the applicator. Examples of these applicator devicesare described in U.S. Pat. No. 4,693,623, to Schwartzman, issued Sep.15, 1987; U.S. Pat. No. 4,620,648, to Schwartzman, issued Sep. 15, 1987;U.S. Pat. No. 3,669,323, to Harker et at., issued Jun. 13, 1972; U.S.Pat. No. 3,418,055, to Schwartzman, issued Dec. 24, 1968; and U.S. Pat.No. 3,410,645, to Schwartzman, issued Nov. 12, 1968; all of which areincorporated herein by reference. Examples of applicators useful hereinare commercially available from Dab-O-Matic, Mount Vernon, N.Y.

Methods for Regulating Hair Growth

The subject invention provides for the use of dyphylline for preventinghair loss. Such prophylactic application is particularly useful toindividuals who have a family history of baldness. In anotherembodiment, the subject invention provides for the use of dyphylline forstimulating new hair growth. Preferably, dyphylline is applied tomammals in need of hair growth regulation, more preferably to mammalssuffering from hair loss. The following methods of use may be used toregulate hair growth.

The compositions according to the invention are preferably intended forapplication by cutaneous injection. The amount of the composition andthe frequency of cutaneous injection can vary widely, depending onpersonal needs. As an example of application by cutaneous injection, itis suggested that a composition suitable for cutaneous injectioncomprising dyphylline be cutaneously injected preferably from about onceper day to about once every six months, more preferably from about twiceper week to about twice per month. The composition for cutaneousinjection will preferably administer from about 0.01 to about 1 mg ofdyphylline per cm² skin receiving cutaneous injection, more preferablyfrom about 0.02 to about 0.5 mg/cm², more preferably still from about0.05 to about 0.1 mg/cm². The period of injections would be over aperiod of from about one month to the life of the subject, morepreferably, in the case of humans, from about 1 month to about tenyears, more preferably from about three months to about two years, morepreferably still from about six months to about one year, therebyresulting in regulation of hair growth.

A more preferred method of applying the compositions according to thesubject invention involves topical application to the scalp of a humansubject or the skin of a domesticated animal subject to regulate hairgrowth, particularly where the scalp/skin is already bald or balding.The amount of the composition and the frequency of application to thehair and/or scalp/skin can vary widely, depending on the desired effectand/or personal needs, but it is suggested as an example that topicalapplication preferably range from about 1 to about 10 times daily, morepreferably from about 1 to about 6 times daily, more preferably stillfrom about 1 to about 3 times daily, and most preferably about once perday.

The composition for topical application will preferably contain fromabout 0.01 to about 1,000 μg of dyphylline per cm² skin receiving thetopical composition, more preferably from about 0.1 to about 600 μg/cm²,more preferably still from about 1 to about 300 μg/cm², more preferablyfrom about 100 to about 300 μg/cm². The period of topical applicationmay be over the subject's life, but would preferably, in the case of ahuman subject, be over a period of from about one month to about tenyears, more preferably from about three months to about two years, morepreferably still from about six months to about one year, therebyresulting in regulation of hair growth.

In another embodiment of the subject invention, hair growth regulationis achieved by topical administration of a composition of the subjectinvention and oral administration of an antiandrogen (e.g., finasteride,cyproterone acetate) during the same treatment period.

Examples

The composition embodiments of the subject invention are illustrated inthe following examples. All parts, percentages, and ratios used hereinare by weight unless otherwise specified.

Example I

An injectable composition is prepared by combining the followingcomponents utilizing conventional mixing techniques.

    ______________________________________                                                             Example No.                                              Component            23                                                       ______________________________________                                        Dyphylline           2.0                                                      Sodium chloride      0.9                                                      Sterile water for injection, USP                                                                   q.s. to 100%                                             ______________________________________                                    

0.1 cc of the composition per cm² skin is injected at the site ofdesired hair regulation once every two weeks for six months to a subjectresulting in new hair growth.

Examples II-IV

The following topical solutions are prepared by combining the followingcomponents utilizing conventional mixing techniques.

    ______________________________________                                                     Example No.                                                      Component      24         25     26                                           ______________________________________                                        Dyphylline     0.01       1.00   5.00                                         N-octyl pyrrolidone                                                                          1.00       3.00   5.00                                         Perfume        1.00       1.00   1.00                                         Dimethyl isosorbide                                                                          balance to 100%                                                ______________________________________                                    

1000 mg of the composition per 100 cm² skin is topically applied twiceper day for one year to a subject resulting in new hair growth.

Examples V-VII

The following conditioning lotions are prepared by combining thefollowing components utilizing conventional mixing techniques.

    ______________________________________                                                            Example No.                                               Component             27     28       29                                      ______________________________________                                        Dyphylline            0.01   1.00     5.00                                    Ammonium laureth sulfate                                                                            6.00   6.00     6.00                                    Disodium cocoamphodiacetate                                                                         3.00   3.00     3.00                                    Alkyl polyglucosides  2.70   2.70     2.70                                    Glycerine             5.00   5.00     5.00                                    Dimethicone copolyol  2.00   2.00     2.00                                    Polyol alkoxy ester   1.20   1.20     1.20                                    Polyquat 10           1.00   1.00     1.00                                    Sodium benzoate       0.25   0.25     0.25                                    DNMM hydantoin*       0.14   0.14     0.14                                    Disodium EDTA**       0.13   0.13     0.13                                    Mineral oil           4.00   4.00     4.00                                    Myristic acid         1.10   1.10     1.10                                    Polyethylene glycol caprylic/capric                                                                 2.00   2.00     2.00                                    glycerides                                                                    Titanium doxide       0.10   0.10     0.10                                    Perfume               1.00   1.00     1.00                                    Water                 balance to 100%                                         ______________________________________                                         *1,3-dihydroxymethyl-3,3-dimethyl hydantoin                                   **ethylenediaminetetraacetic acid                                        

1000 mg of the composition per 100 cm² skin is topically applied onceper day for 6 months to a subject resulting in prevention of hair loss.

Examples VIII-X

The following shampoo compositions are prepared by combining thefollowing components utilizing conventional mixing techniques.

    ______________________________________                                                         Example No.                                                  Component          30       31     32                                         ______________________________________                                        Dyphylline         0.01     1.00   5.00                                       Ammonium laureth sulfate                                                                         6.00     6.00   6.00                                       Disodium cocoamphodiacetate                                                                      3.00     3.00   3.00                                       Alkyl polyglucosides                                                                             2.70     2.70   2.70                                       Glycerine          5.00     5.00   5.00                                       Dimethicone copolyol                                                                             2.00     2.00   2.00                                       Polyol alkoxy ester                                                                              1.20     1.20   1.20                                       Polyquat 10        1.00     1.00   1.00                                       Sodium benzoate    0.25     0.25   0.25                                       DMDM hydantoin*    0.14     0.14   0.14                                       Disodium EDTA**    0.13     0.13   0.13                                       Titanium dioxide   0.10     0.10   0.10                                       Perfume            1.00     1.00   1.00                                       Water              balance to 100%                                            ______________________________________                                         *1,3-dihydroxymethyl-3,3-dimethyl hydantoin                                   **ethylenediaminetetraacetic acid                                        

This composition may be used in a conventional manner for cleaning hair,while bestowing hair growth regulation to the subject. From about 0.1 gto about 10 g of the composition is applied to hair that has beenwetted, generally with water, worked through the hair and then rinsedout.

While particular embodiments of the subject invention have beendescribed, it will be obvious to those skilled in the art that variouschanges and modifications of the subject invention can be made withoutdeparting from the spirit and scope of the invention. It is intended tocover, in the appended claims, all such modifications that are withinthe scope of the invention.

Examples XI-XIII

The following topical solutions are prepared by combining the followingcomponents utilizing conventional mixing techniques.

    ______________________________________                                                    Example No.                                                       Component     33          34     35                                           ______________________________________                                        Dyphylline    1.00        3.00   5.00                                         Propylene glycol                                                                            49.00       47.00  35.00                                        Ethanol       30.00       30.00  30.00                                        Water         20.00       20.00  30.00                                        ______________________________________                                    

1000 mg of the composition per 100 cm² of skin is topically applied onceper day for six months to a subject resulting in new hair growth.

Examples XIV-XVII

The following vanishing creams are prepared by combining the followingcomponents utilizing conventional mixing techniques.

    ______________________________________                                                       Example No.                                                    Component        36     37     38       39                                    ______________________________________                                        Dyphylline       3.00   3.00   3.00     3.00                                  Stearic acid     13.00  7.00   14.00                                          Stearyl alcohol  1.00   5.00                                                  Cetyl alcohol    1.00   2.00   2.00                                           Glyceryl monostearate                   10.00                                 Isopropyl palmitrate           2.00                                           Lanolin                                 2.00                                  Methyl paraben   0.10   0.10   0.10     0.10                                  Sorbitan monostearate          2.00                                           Potassium hydroxide                                                                            0.90                                                         Sodium lauryl sulfate   1.00                                                  Polysorbate 60                 1.50                                           Stearyl colamino formyl                 1.50                                  methyl pyridinium chloride                                                    Water                          q.s. to 100%                                   ______________________________________                                    

1000 mg of the composition per 100 cm² skin is topically applied twiceper day for six months to a subject resulting in new hair growth.

Examples XVIII-XX

The following penetrating creams are prepared by combining the followingcomponents utilizing conventional mixing techniques.

    ______________________________________                                                       Example No.                                                    Component        40       41        42                                        ______________________________________                                        Dyphylline       0.01     1.00      5.00                                      Cetearyl alcohol 5.00     5.00      5.00                                      Silicone oil, 200 fluid                                                                        1.00     1.00      1.00                                      Isopropyl myristate                                                                            2.00     2.00      2.00                                      Sodium stearoyl-2-lactylate                                                                    2.00     2.00      2.00                                      Propylene glycol 5.00     5.00      5.00                                      Sodium citrate   0.2      0.2       0.2                                       Preservative     q.s.     q.s.      q.s.                                      Water                     q.s. to 100                                         ______________________________________                                    

1000 mg of the composition per 100 cm² ski is topically applied once perday for one year to a subject resulting in new hair growth.

Examples XXI-XXIII

The following ion pair oil-in-water emulsions are prepared by combiningthe following components utilizing conventional mixing techniques.

    ______________________________________                                                           Example No.                                                Component            43     44        45                                      ______________________________________                                        Dyphylline           0.01   1.00      5.00                                    Pemuten Tr-2         0.30   0.30      0.30                                    Distearyl dimethyl ammonium chloride                                                               0.15   0.15      0.15                                    Mineral oil          6.0    6.0       6.0                                     Dimethyl isosorbide  6.0    6.0       6.0                                     Dioctyl malate       6.0    6.0       6.0                                     Cetyl alcohol        1.0    1.0       1.0                                     Stearyl alcohol      1.0    1.0       1.0                                     Triethanolamine      0.50   0.50      0.50                                    Water                       q.s. to 100                                       ______________________________________                                    

1000 mg of the composition per 100 cm² of the skin is topically appliedtwice per day for six months to a subject resulting in new hair growth.

Examples XXIV-XXVI

The following liposomal dispersions are prepared by combining thefollowing components utilizing conventional mixing techniques.

    ______________________________________                                                          Example No.                                                 Component           46        47                                              ______________________________________                                        Dyphylline          5.00      5.00                                            Phosphatidyl choling (soy)                                                                        5.00                                                      Cholesterol         0.5       1.00                                            Polyoxyethylene cetylether    5.00                                            Polyoxyehtylene cetyl amine   5.00                                            Alpha-tocapherol    1.0                                                       EDTA                0.1       0.1                                             Water               q.s. to 100                                               ______________________________________                                    

The reagents are blended to produce unilamillar or multilamellarvesicles by methods known to those skilled in the art. The resultingdispersions are either directly applied topically to the scalp (100 mgof composition per 100 cm² of skin) or are blended into a suitableoil-in-water emulsion carrier, e.g, those in Examples V-VII, XIV, XVI,XVIII-XX at a level of about 1-25% (w/w) and then applied topically tothe scalp at a comparable dosage level.

What is claimed is:
 1. A method of regulating hair growth in mammalscomprising applying to a mammal in need of treatment a compositioncomprising:a) a safe and effective amount of dyphylline, having thestructure: ##STR2## or a pharmaceutically-acceptable salt thereof; andb) a carrier.
 2. The method of claim 1 wherein application of thecomposition is by subcutaneous injection.
 3. The method of claim 1wherein application of the composition is topical.
 4. The method ofclaim 3 wherein the amount of dyphylline applied to the skin is fromabout 0.01 μg per cm² skin to about 600 μg per cm² skin.
 5. The methodof claim 4 wherein the amount of dyphylline applied to the skin is fromabout 0.1 μg per cm² skin to about 600 μg per cm² skin.
 6. The method ofclaim 4 wherein the amount of dyphylline applied to the skin is from 1μg per cm² skin to about 300 μg per cm² skin.
 7. A fluid dispensingdevice comprising:a) a fluid container with a mouth; b) a soft,porous-tipped applicator at an end of the fluid container; c) a meansfor holding the applicator in the mouth of the container; and d) aliquid composition deliverable from the fluid container through theapplicator onto the skin, comprising from about 0.005% to about 15% of acompound having the structure: ##STR3## or a pharmaceutically-acceptablesalt thereof.
 8. The device of claim 7 wherein the liquid compositionfurther comprises a phosphodiesterase inhibitor.
 9. The device of claim7 wherein the liquid composition comprises from about 1% to about 3% ofdyphylline.
 10. The device of claim 7 wherein the liquid compositionfurther comprises cyclic adenosine monophosphate or a derivativethereof.
 11. The method of claim 1 wherein the composition comprises atopical carrier comprising an emollient.
 12. The method of claim 1wherein the composition comprises from about 0.005% to about 15%dyphylline.
 13. The method of claim 1 wherein the topical carrierfurther comprises glycerine.
 14. The method of claim 13 wherein thetopical carrier comprises from about 45% to about 85% water.
 15. Themethod of claim 14 wherein the composition comprises from about 1% toabout 10% dyphylline.
 16. The method of claim 15 wherein the compositioncomprises from about 1% to about 5% dyphylline.
 17. A topicalcomposition for regulating hair growth in mammalian skin comprising:a) asafe and effective amount of dyphylline having the structure: ##STR4##or a pharmaceutically-acceptable salt thereof; and b) a topical carriercomprising finasteride.